This research project was planned to define molecular mechanisms and metabolic pathways involved with the process of conversion of very low density lipoproteins (VLDL) and chylomicrons to low density lipoproteins (LDL) and high density lipoproteins (HDL). It has been postulated that the LDL and the HDL represent end products of the non-triglyceride constituents of VLDL and chylomicrons which are not metabolized during fat transport. According to this hypothesis, LDL is derived from core-constituents, and HDL from surface constituents of the triglyceride-rich lipoproteins. Both the LDL and HDL therefore are products of lipoprotein lipase mediated triglyceride hydrolysis in VLDL and chylomicrons. The studies carried out during the first 22 months of the project have established several mechanisms relevant to LDL and HDL formation. 1. We have shown that different LDL particles are formed from different VLDL and chylomicron precursors. Some LDL contain 2-3 fold more cholesterol ester than others, depending on the cholesterol ester content of the precursor VLDL. 2. A unique pathway for re-modelling of LDL (? and HDL) has been elucidated. In this path, LDL cholesterol esters are replaced by triglycerides and the exchanged triglycerides are hydrolyzed by lipoprotein lipase. This process results in a decreased cholesterol ester content of the lipoprotein. 3. LDL-like and HDL precursors were formed in vitro from VLDL lipolysis by a variety of lipases, including one devoid of phospholipase activity. Triglyceride hydrolysis alone therefore is responsible for the formation of these lipoproteins. 4. Normal lipolysis and triglyceride transport are detrimental for HDL formation and for normal HDL subpopulation distribution. Studies in abetalipoproteinemia serve as an outstanding model to study processes involved with the formation of the HDL system.